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恩诺沙星、达氟沙星和马波沙星在日本鹌鹑(Coturnix coturnix japonica)静脉注射和口服给药后的比较药代动力学

Comparative pharmacokinetics of enrofloxacin, danofloxacin, and marbofloxacin after intravenous and oral administration in Japanese quail (Coturnix coturnix japonica).

作者信息

Haritova Aneliya, Dimitrova Dimitrichka, Dinev Toncho, Moutafchieva Rumyana, Lashev Lubomir

机构信息

Department of Pharmacology, Physiology of Animals and Physiological Chemistry, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria.

出版信息

J Avian Med Surg. 2013 Mar;27(1):23-31. doi: 10.1647/2011-032.

Abstract

A population approach was used to evaluate the pharmacokinetic parameters of 3 fluoroquinolones administered to Japanese quail (Coturnix coturnix japonica). Healthy adult quail (n = 50) were divided into 3 groups, each administered a separate intravenous and oral dose of the compounded drug: enrofloxacin at 10 mg/kg (n = 18; 9 male, 9 female), danofloxacin at 10 mg/kg (n = 12; 6 male, 6 female), and marbofloxacin at 5 mg/kg (n = 20; 10 male, 10 female). A fourth group was used as a control (n = 5). Enrofloxacin was metabolized extensively to ciprofloxacin, while no metabolites of either danofloxacin or marbofloxacin were detected. The volume of distribution was high, greater than 1 in all cases, and highest for danofloxacin, followed by enrofloxacin, then marbofloxacin. The total body clearance was higher in quail than that reported for other avian species with the exception of ostriches. As in mammals, the lowest clearance rate of the 3 fluoroquinolones was observed for marbofloxacin. Enrofloxacin was absorbed most rapidly, followed by marbofloxacin, then danofloxacin. The highest bioavailability was observed for danofloxacin followed by marbofloxacin, while very low bioavailability with significant conversion to ciprofloxacin was observed for enrofloxacin. Population analysis showed low intersubject variability for danofloxacin and marbofloxacin in contrast to that for enrofloxacin and its main metabolite, ciprofloxacin. Because of their more favorable pharmacokinetic properties after oral administration, either danofloxacin or marbofloxacin appears to be preferable to enrofloxacin for the treatment of susceptible bacterial infection in Japanese quail.

摘要

采用群体方法评估了三种氟喹诺酮类药物给予日本鹌鹑(Coturnix coturnix japonica)后的药代动力学参数。健康成年鹌鹑(n = 50)分为3组,每组分别静脉注射和口服复合药物:恩诺沙星10 mg/kg(n = 18;9只雄性,9只雌性)、达氟沙星10 mg/kg(n = 12;6只雄性,6只雌性)和马波沙星5 mg/kg(n = 20;10只雄性,10只雌性)。第四组用作对照(n = 5)。恩诺沙星广泛代谢为环丙沙星,而未检测到达氟沙星或马波沙星代谢产物。分布容积较高,在所有情况下均大于1,达氟沙星最高,其次是恩诺沙星,然后是马波沙星。鹌鹑的全身清除率高于除鸵鸟外的其他禽类报道值。与哺乳动物一样,三种氟喹诺酮类药物中马波沙星的清除率最低。恩诺沙星吸收最快,其次是马波沙星,然后是达氟沙星。达氟沙星的生物利用度最高,其次是马波沙星,而恩诺沙星的生物利用度非常低,且大量转化为环丙沙星。群体分析显示,与恩诺沙星及其主要代谢产物环丙沙星相比,达氟沙星和马波沙星的个体间变异性较低。由于口服给药后具有更有利的药代动力学特性,达氟沙星或马波沙星在治疗日本鹌鹑易感细菌感染方面似乎比恩诺沙星更可取。

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